The biotechnology industry makes advances by gaining an increased understanding of known molecules, identifying new molecules and exposing both known and new molecules to different environments. When striving to make these advances, one rate limiting step is the ability by which to obtain molecules of interest.
By way of example, the rate of advances in RNA interference (“RNAi”) has in part been affected by the ability to obtain molecules of interest both efficiently and cost-effectively. The molecules of interest in this field are most often double stranded ribonucleic acids (“dsRNAs”). In mammalian systems, because long dsRNAs will induce a cellular stress response, thereby preventing targeted gene-silencing, typically researchers prefer to work with short interfering ribonucleic acids (“siRNAs,” also known as “small interfering ribonucleic acids”), which are double stranded, but are of a limited size.
siRNAs may be formed either from two separate oligonucleotide strands that anneal or from a single stranded oligonucleotide that forms a hairpin. In either case, preferably there is a duplex region over which each strand is 18-30 nucleotides long. This duplex region, when exposed to endogenous mammalian cellular machinery, causes silencing of one or more genes that contain a sequence that is complementary to the antisense region of the siRNA.
As the use of siRNA has become more common, so too has the desire to generate both genome wide and unique collections of siRNA molecules. Unfortunately, siRNA synthesis is expensive. In order for manufacturers to generate siRNA molecules economically, they need to make them on a large scale. However, most researchers do not require large quantities of siRNA molecules. Therefore, often only a small fraction of what is produced for a particular siRNA duplex or sequence is sold to an individual customer. The remaining siRNA molecules, those beyond what a customer orders, must be stored cold, which presents a considerable burden for the manufacturer with respect to all unsold product. A similar challenge is presented when seeking to obtain other types of molecules for other applications.
Accordingly, there is a need to be able to store libraries of templates for oligonucleotides and to generate selected molecules of interest cost-effectively from these libraries. Various embodiments of the present invention are directed to this need.